Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)predisposition syndrome,characterized by a high mutational burden and microsatellite instability-high(MSI-H)tumors.Immunology of LS-associated CRC(...Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)predisposition syndrome,characterized by a high mutational burden and microsatellite instability-high(MSI-H)tumors.Immunology of LS-associated CRC(LS-CRC)is unique,with significant implications for treatment.Despite well-established knowledge of LS immunology,immunotherapy dose and treatment response can vary significantly based on local tumor immunity and specific germline pathogenic variant of LS genes.This variability necessitates tailored surveillance strategies and new personalised immunotherapy approaches for LS patients.LS-CRC often benefits from immunotherapy due to the distinct tumor microenvironment(TME)and the variety of tumor infiltrating lymphocytes(TILs).This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images(WSIs)that accounts for the distinct TME of LS-CRC.By emphasizing the necessity of personalized medicine in hereditary cancer syndromes,the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.展开更多
An ionic liquid ion source(ILIS)is a kind of high brightness ion source capable of providing high-speed positive or negative ion beams.This paper presents a miniaturized ILIS based on an array of porous metal strips.T...An ionic liquid ion source(ILIS)is a kind of high brightness ion source capable of providing high-speed positive or negative ion beams.This paper presents a miniaturized ILIS based on an array of porous metal strips.The porous emitter array,integrated with seven 10 mm long strips,is fabricated using wire electrical discharge machining(WEDM)combined with electrochemical etching.The assembled ILIS is 30 mm×30 mm×17.5 mm in size and weighs less than 25 g.A series of experiments,including anⅠ-Ⅴcharacteristic test,a retarding potential analyzer(RPA)test,and a spatial plume distribution test,have been conducted in vacuo to characterize the performance of the ILIS.Results show that the emitted current is up to about 800μA and ion transparency is as high as 94%.Besides,RPA curves reveal that the total fragmentation rate of the emitted particles accounts for 48.8%in positive mode and 59.8%in negative mode.Further,with the increase in applied acceleration voltage,the voltage loss rises while the energy efficiency decreases.It is also found that the plume perpendicular to the strips has a higher divergence than the one parallel to the strips.A numerical simulation by COMSOL reveals that the electric field distribution between the two electrodes results in such a spatial plume profile.展开更多
A novel method based on wavelength-multiplexed line-of-sight absorption and profile fitting for nonuniform flow field measurement is reported. A wavelength scanning combing laser temperature and current modulation WMS...A novel method based on wavelength-multiplexed line-of-sight absorption and profile fitting for nonuniform flow field measurement is reported. A wavelength scanning combing laser temperature and current modulation WMS scheme is used to implement the wavelength-multi- plexed-profile fitting method. Second harmonic （2f） signal of eight H20 transitions features near 7,170 cm^-1 are measured in one period using a single tunable diode laser. Spatial resolved temperature distribution upon a CH4/air premixed flat flame burner is obtained. The result validates the feasibility of strategy for non-uniform flow field diagnostics by means of WMS-2f TDLAS.展开更多
Stimulated Brillouin scattering(SBS)-induced mode distortion(MD)in high power narrow linewidth fiber amplifiers has been implemented,and the origin has been investigated from the aspect of the evolution of the optical...Stimulated Brillouin scattering(SBS)-induced mode distortion(MD)in high power narrow linewidth fiber amplifiers has been implemented,and the origin has been investigated from the aspect of the evolution of the optical spectrum,spatial beam profiles,and temporal-frequency domain characteristics.展开更多
A simple and effective approach is proposed to minimize the effect of unmodulated light and uneven intensity caused by the pixelated structure of the spatial light modulator in a holographic display. A more uniform im...A simple and effective approach is proposed to minimize the effect of unmodulated light and uneven intensity caused by the pixelated structure of the spatial light modulator in a holographic display. A more uniform image is produced by purposely shifting the holographic images of multiple reconstructed lights with different incident angles from the zero-diffraction-order and overlapping those selected different orders. The simulation and optical experimental results show that the influence of the zero-diffraction-order can be reduced, while keeping the good uniformity of the target images by this new approach.展开更多
Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities.To overview the specificity of cell signaling,we integrated human re...Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities.To overview the specificity of cell signaling,we integrated human receptome data with proteome spatial expression profiles to systematically investigate the specificity of receptors and receptor-triggered transduction networks across 62 normal cell types and 14 cancer types.Six percent receptors showed cell-type-specific expression,and 4% signaling networks presented enriched cell-specific proteins induced by the receptors.We introduced a concept of“response context”to annotate the cell-type dependent signaling networks.We found that most cells respond similarly to the same stimulus,as the“response contexts”presented high functional similarity.Despite this,the subtle spatial diversity can be observed from the difference in network architectures.The architecture of the signaling networks in nerve cells displayed less completeness than that in glandular cells,which indicated cellular-context dependent signaling patterns are elaborately spatially organized.Likewise,in cancer cells most signaling networks were generally dysfunctional and less complete than that in normal cells.However,glioma emerged hyper-activated transduction mechanism in malignant state.Receptor ATP6AP2 and TNFRSF21 induced rennin-angiotensin and apoptosis signaling were found likely to explain the glioma-specific mechanism.This work represents an effort to decipher context-specific signaling network from spatial dimension.Our results indicated that although a majority of cells engage general signaling response with subtle differences,the spatial dynamics of cell signaling can not only deepen our insights into different signaling mechanisms,but also help understand cell signaling in disease.展开更多
文摘Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)predisposition syndrome,characterized by a high mutational burden and microsatellite instability-high(MSI-H)tumors.Immunology of LS-associated CRC(LS-CRC)is unique,with significant implications for treatment.Despite well-established knowledge of LS immunology,immunotherapy dose and treatment response can vary significantly based on local tumor immunity and specific germline pathogenic variant of LS genes.This variability necessitates tailored surveillance strategies and new personalised immunotherapy approaches for LS patients.LS-CRC often benefits from immunotherapy due to the distinct tumor microenvironment(TME)and the variety of tumor infiltrating lymphocytes(TILs).This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images(WSIs)that accounts for the distinct TME of LS-CRC.By emphasizing the necessity of personalized medicine in hereditary cancer syndromes,the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.
基金supported by National Natural Science Foundation of China(No.52075334)。
文摘An ionic liquid ion source(ILIS)is a kind of high brightness ion source capable of providing high-speed positive or negative ion beams.This paper presents a miniaturized ILIS based on an array of porous metal strips.The porous emitter array,integrated with seven 10 mm long strips,is fabricated using wire electrical discharge machining(WEDM)combined with electrochemical etching.The assembled ILIS is 30 mm×30 mm×17.5 mm in size and weighs less than 25 g.A series of experiments,including anⅠ-Ⅴcharacteristic test,a retarding potential analyzer(RPA)test,and a spatial plume distribution test,have been conducted in vacuo to characterize the performance of the ILIS.Results show that the emitted current is up to about 800μA and ion transparency is as high as 94%.Besides,RPA curves reveal that the total fragmentation rate of the emitted particles accounts for 48.8%in positive mode and 59.8%in negative mode.Further,with the increase in applied acceleration voltage,the voltage loss rises while the energy efficiency decreases.It is also found that the plume perpendicular to the strips has a higher divergence than the one parallel to the strips.A numerical simulation by COMSOL reveals that the electric field distribution between the two electrodes results in such a spatial plume profile.
基金supported by the National Natural Science Foundation of China(10772188)
文摘A novel method based on wavelength-multiplexed line-of-sight absorption and profile fitting for nonuniform flow field measurement is reported. A wavelength scanning combing laser temperature and current modulation WMS scheme is used to implement the wavelength-multi- plexed-profile fitting method. Second harmonic （2f） signal of eight H20 transitions features near 7,170 cm^-1 are measured in one period using a single tunable diode laser. Spatial resolved temperature distribution upon a CH4/air premixed flat flame burner is obtained. The result validates the feasibility of strategy for non-uniform flow field diagnostics by means of WMS-2f TDLAS.
基金National Natural Science Foundation of China(62205317).
文摘Stimulated Brillouin scattering(SBS)-induced mode distortion(MD)in high power narrow linewidth fiber amplifiers has been implemented,and the origin has been investigated from the aspect of the evolution of the optical spectrum,spatial beam profiles,and temporal-frequency domain characteristics.
基金supported by the UK Engineering and Physical Sciences Research Council(EPSRC) for the support through the EPSRC Centre for Innovative Manufacturing in Ultra Precision(EP/I033491/1)
文摘A simple and effective approach is proposed to minimize the effect of unmodulated light and uneven intensity caused by the pixelated structure of the spatial light modulator in a holographic display. A more uniform image is produced by purposely shifting the holographic images of multiple reconstructed lights with different incident angles from the zero-diffraction-order and overlapping those selected different orders. The simulation and optical experimental results show that the influence of the zero-diffraction-order can be reduced, while keeping the good uniformity of the target images by this new approach.
基金kindly funded by National Natural Science Foundation of China(Grant No.31070752)in part supported by the National Basic Research Program(973 Program)(Nos 2011CB910204,2010CB529206 and 2010CB912702)+4 种基金Key Infectious Disease Project(No.2012ZX10002012-014)Research Program of Chinese Academy of Sciences(Nos.KSCX2-EW-R-04,KSCX2-YW-R-190 and 2011KIP204)National Natural Science Foundation of China(Grant No.30900272)Chinese Ministry for Science and Technology Grant(No.2008BAI64B01)the National High Technology Research and Development Program(863 Program)(No.2009AA02Z304).
文摘Studies on cell signaling pay more attention to spatial dynamics and how such diverse organization can relate to high order of cellular capabilities.To overview the specificity of cell signaling,we integrated human receptome data with proteome spatial expression profiles to systematically investigate the specificity of receptors and receptor-triggered transduction networks across 62 normal cell types and 14 cancer types.Six percent receptors showed cell-type-specific expression,and 4% signaling networks presented enriched cell-specific proteins induced by the receptors.We introduced a concept of“response context”to annotate the cell-type dependent signaling networks.We found that most cells respond similarly to the same stimulus,as the“response contexts”presented high functional similarity.Despite this,the subtle spatial diversity can be observed from the difference in network architectures.The architecture of the signaling networks in nerve cells displayed less completeness than that in glandular cells,which indicated cellular-context dependent signaling patterns are elaborately spatially organized.Likewise,in cancer cells most signaling networks were generally dysfunctional and less complete than that in normal cells.However,glioma emerged hyper-activated transduction mechanism in malignant state.Receptor ATP6AP2 and TNFRSF21 induced rennin-angiotensin and apoptosis signaling were found likely to explain the glioma-specific mechanism.This work represents an effort to decipher context-specific signaling network from spatial dimension.Our results indicated that although a majority of cells engage general signaling response with subtle differences,the spatial dynamics of cell signaling can not only deepen our insights into different signaling mechanisms,but also help understand cell signaling in disease.
